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ML-as-a-service continues to grow, and so does the need for very strong privacy guarantees. Secure inference has emerged as a potential solution, wherein cryptographic primitives allow inference without revealing users' inputs to a model provider or model's weights to a user. For instance, the model provider could be a diagnostics company that has trained a state-of-the-art DenseNet-121 model for interpreting a chest X-ray and the user could be a patient at a hospital. While secure inference is in principle feasible for this setting, there are no existing techniques that make it practical at scale. The CrypTFlow2 framework provides a potential solution with its ability to automatically and correctly translate clear-text inference to secure inference for arbitrary models. However, the resultant secure inference from CrypTFlow2 is impractically expensive: Almost 3TB of communication is required to interpret a single X-ray on DenseNet-121. In this paper, we address this outstanding challenge of inefficiency of secure inference with three contributions. First, we show that the primary bottlenecks in secure inference are large linear layers which can be optimized with the choice of network backbone and the use of operators developed for efficient clear-text inference. This finding and emphasis deviates from many recent works which focus on optimizing non-linear activation layers when performing secure inference of smaller networks. Second, based on analysis of a bottle-necked convolution layer, we design a X-operator which is a more efficient drop-in replacement. Third, we show that the fast Winograd convolution algorithm further improves efficiency of secure inference. In combination, these three optimizations prove to be highly effective for the problem of X-ray interpretation trained on the CheXpert dataset., 10 pages include references, 4 figures

Supplemental Digital Content is available in the text., Background: The coronavirus disease 2019 (COVID-19) pandemic has exposed longstanding racial and ethnic inequities in health risks and outcomes in the United States. We aimed to identify racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. Methods: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7868 patients by race/ethnicity treated at 88 hospitals across the United States between January 17, 2020, and July 22, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization alone. Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. Results: Among 7868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios for mortality were 0.93 (95% CI, 0.76–1.14) for Black patients, 0.90 (95% CI, 0.73–1.11) for Hispanic patients, and 1.31 (95% CI, 0.96–1.80) for Asian patients compared with non-Hispanic White patients. The median odds ratio across hospitals was 1.99 (95% CI, 1.74–2.48). Results were similar for major adverse cardiovascular events. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted odds ratio, 1.48 [95% CI, 1.16–1.90]). Conclusions: Although in-hospital mortality and major adverse cardiovascular events did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity because of their disproportionate representation among COVID-19 hospitalizations.

A versatile air insulated high current medium energy 200 kV Ion Accelerator has been running successfully at Ion Beam Centre, Kurukshetra University, India for carrying out multifarious experiments in material science and surface physics. Ion beam induced structures on the surfaces of semiconductors have potential applications in photonics, magnetic devices, photovoltaics, and surface-wetting tailoring etc. In this regard, silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. In the present work, fabrication of self-organized ripple patterns is carried out on the SiC surfaces using 80 keV Ar+ ions for different fluences at oblique incidence of 500. Studies demonstrate that ripple wavelength and amplitude, ordering and homogeneity of these patterns vary linearly with argon ion fluence. The ripples tend to align themselves parallel to the projection of the ion beam direction. The evolution of such surface structures is explained with the help of existing formalisms of coupling between surface topography and preferential sputtering., Proceedings of the 13th International Particle Accelerator Conference, IPAC2022, Bangkok, Thailand

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Supplemental material, sj-docx-2-tam-10.1177_17588359221126149 for Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial by Maria-Pilar Barretina-Ginesta, Bradley J. Monk, Sileny Han, Bhavana Pothuri, Annika Auranen, Dana M. Chase, Domenica Lorusso, Charles Anderson, Sophie Abadie-Lacourtoisie, Noelle Cloven, Elena I. Braicu, Amnon Amit, Andrés Redondo, Ruchit Shah, Nehemiah Kebede, Carol Hawkes, Divya Gupta, Tatia Woodward, David M. O’Malley and Antonio González-Martín in Therapeutic Advances in Medical Oncology

Supplemental material, sj-docx-1-tam-10.1177_17588359221126149 for Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial by Maria-Pilar Barretina-Ginesta, Bradley J. Monk, Sileny Han, Bhavana Pothuri, Annika Auranen, Dana M. Chase, Domenica Lorusso, Charles Anderson, Sophie Abadie-Lacourtoisie, Noelle Cloven, Elena I. Braicu, Amnon Amit, Andrés Redondo, Ruchit Shah, Nehemiah Kebede, Carol Hawkes, Divya Gupta, Tatia Woodward, David M. O’Malley and Antonio González-Martín in Therapeutic Advances in Medical Oncology

The β-lactam antibiotics are the most effective medicines for treating bacterial infections. Resistance to them, particularly through the production of β-lactamases, which can hydrolyse all kinds of β-lactams, poses a threat to their continued use. The synthesised flavone and coumarin based isoxazole derivatives have the potential to be used as broad-spectrum inhibitors of the mechanistically different serine-(SBL) and metallo-β-lactamases (MBL). The synthesised compounds were discovered as potent β-lactamase inhibitors using molecular docking and in silico pharmacokinetic analysis. We studied the binding of chemically synthesised inhibitors to clinically significant β-lactamases of class A, B, and C using biophysical and biochemical approaches, and computational analyses. These molecules follow Lipinski’s rule of five and have acceptable solubility, permeability, and oral bioavailability. These molecules were found to be non-toxic and non-carcinogenic. MIC results suggest that these molecules restore the antibiotic efficacy against class A, B, and C β-lactamases. Kinetics data showed that these molecules reduce the catalytic efficiency of clinically relevant class A, B, and C β-lactamases. Fluorescence study showed significant interaction between these flavone-/coumarin-based isoxazole derivatives and class A/B/ C β-lactamases. This study showed promising effect of these new generation compounds as broad spectrum β-lactamase inhibitors of both SBLs and MBLs. Communicated by Ramaswamy H. Sarma

Supplemental material, sj-docx-2-tam-10.1177_17588359221126149 for Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial by Maria-Pilar Barretina-Ginesta, Bradley J. Monk, Sileny Han, Bhavana Pothuri, Annika Auranen, Dana M. Chase, Domenica Lorusso, Charles Anderson, Sophie Abadie-Lacourtoisie, Noelle Cloven, Elena I. Braicu, Amnon Amit, Andrés Redondo, Ruchit Shah, Nehemiah Kebede, Carol Hawkes, Divya Gupta, Tatia Woodward, David M. O’Malley and Antonio González-Martín in Therapeutic Advances in Medical Oncology

Ultraviolet (UV) exposure to the skin causes photo-damage and acts as the primary etiological agent in photo-carcinogenesis. UV-B exposure induces cellular damage and is the major factor challenging skin homeostasis. Autophagy allows the fundamental adaptation of cells to metabolic and oxidative stress. Cellular dysfunction has been observed in aged tissues and in toxic insults to cells undergoing stress. Conversely, promising anti-aging strategies aimed at inhibiting the mTOR pathway have been found to significantly improve the aging-related disorders. Recently, autophagy has been found to positively regulate skin homeostasis by enhancing DNA damage recognition. Here, we investigated the geno-protective roles of autophagy in UV-B-exposed primary human dermal fibroblasts (HDFs). We found that UV-B irradiation to HDFs impairs the autophagy response in a time- and intensity-independent manner. However, improving autophagy levels in HDFs with pharmacological activators regulates the UV-B-induced cellular stress by decreasing the induction of DNA photo-adducts, promoting the DNA repair process, alleviating oxidative and ER stress responses, and regulating the expression levels of key cell cycle regulatory proteins. Autophagy also prevents HDFs from UV-B-induced nuclear damage as is evident in TUNEL assay and Acridine Orange/Ethidium Bromide co-staining. Salubrinal (an eIF2α phosphatase inhibitor) relieves ER stress response in cells and also significantly alleviates DNA damage and promotes the repair process in UV-B-exposed HDFs. P62-silenced HDFs show enhanced DNA damage response and also disturb the tumor suppressor PTEN/pAKT signaling axis in UV-B-exposed HDFs whereas Atg7-silenced HDFs reveal an unexpected consequence by decreasing the UV-B-induced DNA damage. Taken together, these results suggest that interventional autophagy offers significant protection against UV-B radiation-induced photo-damage and holds great promise in devising it as a suitable therapeutic strategy against skin pathological disorders.

BACKGROUND/AIMS Excessive exposure to UV radiation negatively affects the human skin, characterized by photo-damage (premature aging & carcinogenesis). UV-B radiation causes about 90% of non-melanoma skin cancers by damaging de-oxy ribonucleic acids (DNA). We have previously reported that UV-B radiation induces skin photodamage through oxidative & Endoplasmic Reticulum (ER) stresses and Glycyrrhizic acid (GA), a natural triterpene, protects skin cells against such stresses. UV-B radiation elicits signalling cascade by activation of proteins involved in sensing, signalling, and repair process of DNA damage. In this study, we explored the effects & mechanisms of Glycyrrhizic acid (GA) against UV-B -induced photodamage using a well established cellular model. METHODS We used primary human dermal fibroblasts as a cellular model. The cells were cultured in the presence or absence of GA for 3,6, & 24 h. Effect of UV-B was assessed by examining cell viability, cell morphology, oxidative stress, ER stress, DNA damage & cellular autophagy levels through biochemical assays, microscopy & protein expression studies. RESULTS In this study, we have determined the effect of GA on autophagy mediated DNA damage response system as the main mechanism in preventing photodamage due to UV-B -irradiation to primary human dermal fibroblasts (HDFs). GA treatment to UV-B exposed HDFs, significantly inhibited cell death, oxidative & ER stress responses, prevented Cyclobutane Pyrimidine dimer (CPD) DNA adduct formation, and DNA fragmentation via modulation of UV-B induced autophagic flux. Present results showed that GA treatment quenched reactive oxygen species (ROS), relieved ER stress response, improved autophagy (6 hr's post-UV-B -irradiation) and prevented UV-B induced DNA damage. CONCLUSION The present study links autophagy induction by GA as the main mechanism in the prevention of DNA damage and provides a mechanistic basis for the photoprotective effect of GA and suggests that GA can be potentially developed as a promising agent against UV-B induced skin photo-damage.

We present CRYPTFLOW, a system that converts TensorFlow inference code into Secure Multi-party Computation (MPC) protocols at the push of a button. To do this, we build two components. Our first component is an end-to-end compiler from TensorFlow to a variety of MPC protocols. The second component is an improved semi-honest 3-party protocol that provides significant speedups for inference. We empirically demonstrate the power of our system by showing the secure inference of real-world neural networks such as DENSENET121 for detection of lung diseases from chest X-ray images and 3D-UNet for segmentation in radiotherapy planning using CT images. In particular, this paper provides the first evaluation of secure segmentation of 3D images, a task that requires much more powerful models than classification and is the largest secure inference task run till date., 6 pages. PPML NeurIPS 2020 Workshop, Vancouver, Canada. arXiv admin note: substantial text overlap with arXiv:1909.07814

Cutaneous photodamage is incited via exposure of ultraviolet-B (UV-B) radiation to skin, characterized by the manifestation of oxidative stress, inflammation, collagen degradation and apoptosis which translates to external aging signs such as wrinkle formation and leathery skin appearance. Meanwhile, it increases cellular susceptibility to photocarcinogenesis. Several studies have accumulated evidence regarding the usage of natural agents in reversing the clinical signs of photoaging as well as preventing photo-toxicity at molecular level. In this study, we have explored the therapeutic potential of natural agent Trigonelline (TG) against UV-B radiation mediated skin photodamage. Various parameters modulated by the exposure of UV-B radiation were investigated in human skin cells and chronic photodamage mice model (Balb/c). We found that TG alleviates UV-B radiation induced photodamage in human skin cells and Balb/c skin mice. TG treatment in UV-B irradiated skin cells abates UV-B radiation mediated phototoxicity, oxidative stress, inflammation and apoptosis. At molecular level, we observed TG treatment significantly prevents the reactive oxygen species (ROS) generation and lipid peroxidation, restores collagen synthesis and matrix metalloproteinase (MMPs) levels. The in vitro findings were replicated in the in vivo model. We found that the TG acts potentially via modulation of ROS-MAPKs-NF-κB axis. Collectively, we propose that TG acts antagonistically against UV-B mediated skin damage and has strong potential to be developed as a therapeutic and cosmetical agent against photodamage disorders.

The PARADIGM-HF trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in PARADIGM-HF had NYHA class IV symptomology; accordingly, data that informs the use of S/V among patients with advanced HF are limited. The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) study is a 24-week prospective, multicenter, double-blinded, double-dummy, active-comparator trial to assess the safety, efficacy and tolerability of S/V compared with V in patients with advanced HFrEF. The trial planned to randomize 400 patients age ≥18 years with advanced HF, defined as an EF ≤35%, NYHA functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/mL or N-terminal-pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/mL), and ≥1 objective finding(s) of advanced HF. Following a 3-7 day open-label run-in period with S/V 24/26 mg twice daily, patients are randomized 1:1 to S/V titrated to 97/103 mg twice daily versus 160 mg V twice daily. The primary endpoint is the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints include clinical outcomes, as well as safety and tolerability. Because of the COVID-19 pandemic enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis will consist of the first 335 randomized patients, whose clinical follow-up was not severely impacted by COVID-19., Graphical abstract, Highlights • There is limited experience with the use of sacubitril/valsartan (S/V) in patients with advanced HF and NYHA class IV symptoms. • The LIFE (LCZ696 In Hospitalized Advanced Heart FailurE) trial is a 24-week prospective, multicenter, double-blinded, double-dummy, active-comparator trial to assess the safety, efficacy and tolerability of S/ compared with valsartan patients with advanced HFrEF • The overall study protocol and timeline are depicted in the Central Illustration • Enrollment in the LIFE trial was halted prematurely because of the COVID-19 pandemic • The COVID-19 mitigation strategies employed by the LIFE investigators are described

This paper presents EinsteinPy (version 0.3), a community-developed Python package for gravitational and relativistic astrophysics. Python is a free, easy to use a high-level programming language which has seen a huge expansion in the number of its users and developers in recent years. Specifically, a lot of recent studies show that the use of Python in Astrophysics and general physics has increased exponentially. We aim to provide a very high level of abstraction, an easy to use interface and pleasing user experience. EinsteinPy is developed keeping in mind the state of a theoretical gravitational physicist with little or no background in computer programming and trying to work in the field of numerical relativity or trying to use simulations in their research. Currently, EinsteinPy supports simulation of time-like and null geodesics and calculates trajectories in different background geometries some of which are Schwarzschild, Kerr, and KerrNewmann along with coordinate inter-conversion pipeline. It has a partially developed pipeline for plotting and visualization with dependencies on libraries like Plotly, matplotlib, etc. One of the unique features of EinsteinPy is a sufficiently developed symbolic tensor manipulation utilities which are a great tool in itself for teaching yourself tensor algebra which for many beginner students can be overwhelmingly tricky. EinsteinPy also provides few utility functions for hypersurface embedding of Schwarzschild spacetime which further will be extended to model gravitational lensing simulation., We plan to submit it to A&A. 9 pages

We introduce Blockene, a blockchain that reduces resource usage at member nodes by orders of magnitude, requiring only a smartphone to participate in block validation and consensus. Despite being lightweight, Blockene provides a high throughput of transactions and scales to a large number of participants. Blockene consumes negligible battery and data in smartphones, enabling millions of users to participate in the blockchain without incentives, to secure transactions with their collective honesty. Blockene achieves these properties with a novel split-trust design based on delegating storage and gossip to untrusted nodes. We show, with a prototype implementation, that Blockene provides throughput of 1045 transactions/sec, and runs with very low resource usage on smartphones, pointing to a new paradigm for building secure, decentralized applications., Comment: A version of this paper (without the appendix) will appear in OSDI 2020

Objective This prospective randomised double-blind study was conducted to compare the effect of intravenous (IV) with intraperitoneal (IP) administration of clonidine with respect to analgesic efficacy and side effects. Methods A total of 60 American Society of Anaesthesiologists (ASA) physical status class I and II patients, aged 35–60 years, undergoing total abdominal hysterectomy, were randomly divided into 2 groups. Standard general anaesthesia technique was used. All the patients in group IV received 3 μg kg−1 of IV clonidine after resection of the uterus along with 0.25% bupivacaine (20 mL intraperitoneally and 10 mL as wound infiltration), whereas patients in group IP received 10 mL of normal saline intravenously and 3 μg kg−1 of clonidine mixed with 0.25% bupivacaine (20 mL intraperitoneally and 10 mL as wound infiltration). Postoperative analgesia was provided with IV diclofenac every 8 hours and IV fentanyl (1 μg kg−1) on demand. Pain at rest, opioid consumption, level of sedation and severity of nausea were recorded for 24 hours. The heart rate (HR) and blood pressure (BP) were recorded at an interval of 15 minutes for 2 hours followed by routine hourly monitoring. Results Both the groups were found to be similar with respect to demography and ASA physical status. The maximum pain was felt at 6 hours in both the groups. The mean visual analogue scale score at 6 hours (p=0.47) was comparable. However, patients in group IV had significantly higher sedation (p

TPS6101 Background: Despite surgery and CT (paclitaxel + carboplatin ± bevacizumab [bev]), 5-year survival rates remain low for patients (pts) with FIGO stage 3 or 4 OC. Niraparib is a poly (ADP-ribose) polymerase (PARP) inhibitor that has recently demonstrated efficacy in 1L therapy. Dostarlimab (TSR-042) is an anti-programmed death (PD)-1 humanized monoclonal antibody that has shown clinical activity as monotherapy in early phase trials. The currently enrolling ENGOT-OV44/FIRST study will compare efficacy and safety of CT + dostarlimab + niraparib ± bev (Arm 3) vs CT + niraparib ± bev (Arm 2). Methods: Eligible pts are ≥18 years of age, with FIGO stage 3 or 4 non-mucinous epithelial OC, ECOG performance status < 2, and tumor tissue available for PD-1 ligand (PD-L1) testing. After cycle 1 of CT, pts are stratified by concurrent bev use, BRCA mutation/homologous recombination repair status, and disease burden, then randomized 1:2 into trial Arms 2 and 3 (Table). Dostarlimab is administered at 500 mg IV Q3W during the CT period, then 1000 mg IV Q6W during the maintenance period. Niraparib dosing is 200 mg PO QD for pts with baseline bodyweight (BW) < 77 kg and/or platelet count (PC) < 150,000/µL, or 300 mg QD for pts with baseline BW ≥77 kg and PC ≥150,000/µL. The dual primary endpoints are PFS, based on investigator assessment per RECIST v1.1, in both PD-L1+ and all patients. Initially the study enrolled pts to Arm 1. This arm was discontinued following positive results from the PRIMA/ENGOT-OV26/GOG-3012 and PAOLA-1/ENGOT-OV25 studies. This allows investigators to offer the current standard of care to all patients. Clinical trial information: NCT03602859, EUDRACT 2018-000413-20. [Table: see text]

The discovery of NDM-1 and its variants has caused the emergence of antibiotic resistance in the community and hospital setting, causing major concern for health care across the globe. New Delhi Metallo-β-lactamase is known to hydrolyse almost all β-lactam antibiotics. Studies have shown the hydrolytic activates of NDM-1 and some of its variants, however a comparative study of these NDM variants has not been explored in detail. Hence, we proposed to check their catalytic activity by performing a comparative study between NDM-1 and its variants. The study was initiated to clone NDM variants (NDM-1, NDM-4, NDM-5, NDM-6 and NDM-7) followed by overexpression of the recombinant proteins to check their hydrolytic properties against β-lactam antibiotics. The minimum inhibitory concentration of carbapenems antibiotics for blaNDM-5 clone was found four fold increased, whereas no change was observed in the clones having other variants. The hydrolytic activity of carbapenem with NDM-5 variant was found to be augmented as per the kinetics parameter where Km was decreased and kcat, kcat/Km values increased as compared to the NDM-1. Molecular docking studies were employed to identify the variations in the binding ability among all NDM variants with imipenem or meropenem. Simulation studies at 100 ns showed a good stability of NDM-5 with imipenem and meropenem as compared to NDM-1. CD spectroscopy data revealed significant changes in the secondary structure of NDM variants. We conclude that NDM-5 showed higher hydrolytic activity as compared to other variants. This study provides a comparative analysis of the severity of NDM producing strains.

Interview guide. (DOCX 16 kb)

Table of contents A1 Introduction to the 8th Annual Conference on the Science of Dissemination and Implementation: Optimizing Personal and Population Health David Chambers, Lisa Simpson D1 Discussion forum: Population health D&I research Felicia Hill-Briggs D2 Discussion forum: Global health D&I research Gila Neta, Cynthia Vinson D3 Discussion forum: Precision medicine and D&I research David Chambers S1 Predictors of community therapists’ use of therapy techniques in a large public mental health system Rinad Beidas, Steven Marcus, Gregory Aarons, Kimberly Hoagwood, Sonja Schoenwald, Arthur Evans, Matthew Hurford, Ronnie Rubin, Trevor Hadley, Frances Barg, Lucia Walsh, Danielle Adams, David Mandell S2 Implementing brief cognitive behavioral therapy (CBT) in primary care: Clinicians' experiences from the field Lindsey Martin, Joseph Mignogna, Juliette Mott, Natalie Hundt, Michael Kauth, Mark Kunik, Aanand Naik, Jeffrey Cully S3 Clinician competence: Natural variation, factors affecting, and effect on patient outcomes Alan McGuire, Dominique White, Tom Bartholomew, John McGrew, Lauren Luther, Angie Rollins, Michelle Salyers S4 Exploring the multifaceted nature of sustainability in community-based prevention: A mixed-method approach Brittany Cooper, Angie Funaiole S5 Theory informed behavioral health integration in primary care: Mixed methods evaluation of the implementation of routine depression and alcohol screening and assessment Julie Richards, Amy Lee, Gwen Lapham, Ryan Caldeiro, Paula Lozano, Tory Gildred, Carol Achtmeyer, Evette Ludman, Megan Addis, Larry Marx, Katharine Bradley S6 Enhancing the evidence for specialty mental health probation through a hybrid efficacy and implementation study Tonya VanDeinse, Amy Blank Wilson, Burgin Stacey, Byron Powell, Alicia Bunger, Gary Cuddeback S7 Personalizing evidence-based child mental health care within a fiscally mandated policy reform Miya Barnett, Nicole Stadnick, Lauren Brookman-Frazee, Anna Lau S8 Leveraging an existing resource for technical assistance: Community-based supervisors in public mental health Shannon Dorsey, Michael Pullmann S9 SBIRT implementation for adolescents in urban federally qualified health centers: Implementation outcomes Shannon Mitchell, Robert Schwartz, Arethusa Kirk, Kristi Dusek, Marla Oros, Colleen Hosler, Jan Gryczynski, Carolina Barbosa, Laura Dunlap, David Lounsbury, Kevin O'Grady, Barry Brown S10 PANEL: Tailoring Implementation Strategies to Context - Expert recommendations for tailoring strategies to context Laura Damschroder, Thomas Waltz, Byron Powell S11 PANEL: Tailoring Implementation Strategies to Context - Extreme facilitation: Helping challenged healthcare settings implement complex programs Mona Ritchie S12 PANEL: Tailoring Implementation Strategies to Context - Using menu-based choice tasks to obtain expert recommendations for implementing three high-priority practices in the VA Thomas Waltz S13 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Siri, rate my therapist: Using technology to automate fidelity ratings of motivational interviewing David Atkins, Zac E. Imel, Bo Xiao, Doğan Can, Panayiotis Georgiou, Shrikanth Narayanan S14 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Identifying indicators of implementation quality for computer-based ratings Cady Berkel, Carlos Gallo, Irwin Sandler, C. Hendricks Brown, Sharlene Wolchik, Anne Marie Mauricio S15 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Improving implementation of behavioral interventions by monitoring emotion in spoken speech Carlos Gallo, C. Hendricks Brown, Sanjay Mehrotra S16 Scorecards and dashboards to assure data quality of health management information system (HMIS) using R Dharmendra Chandurkar, Siddhartha Bora, Arup Das, Anand Tripathi, Niranjan Saggurti, Anita Raj S17 A big data approach for discovering and implementing patient safety insights Eric Hughes, Brian Jacobs, Eric Kirkendall S18 Improving the efficacy of a depression registry for use in a collaborative care model Danielle Loeb, Katy Trinkley, Michael Yang, Andrew Sprowell, Donald Nease S19 Measurement feedback systems as a strategy to support implementation of measurement-based care in behavioral health Aaron Lyon, Cara Lewis, Meredith Boyd, Abigail Melvin, Semret Nicodimos, Freda Liu, Nathanial Jungbluth S20 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Common loop assay: Methods of supporting learning collaboratives Allen Flynn S21 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Innovating audit and feedback using message tailoring models for learning health systems Zach Landis-Lewis S22 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Implementation science and learning health systems: Connecting the dots Anne Sales S23 Facilitation activities of Critical Access Hospitals during TeamSTEPPS implementation Jure Baloh, Marcia Ward, Xi Zhu S24 Organizational and social context of federally qualified health centers and variation in maternal depression outcomes Ian Bennett, Jurgen Unutzer, Johnny Mao, Enola Proctor, Mindy Vredevoogd, Ya-Fen Chan, Nathaniel Williams, Phillip Green S25 Decision support to enhance treatment of hospitalized smokers: A randomized trial Steven Bernstein, June-Marie Rosner, Michelle DeWitt, Jeanette Tetrault, James Dziura, Allen Hsiao, Scott Sussman, Patrick O’Connor, Benjamin Toll S26 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A patient-centered approach to successful community transition after catastrophic injury Michael Jones, Julie Gassaway S27 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - Conducting PCOR to integrate mental health and cancer screening services in primary care Jonathan Tobin S28 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A comparative effectiveness trial of optimal patient-centered care for US trauma care systems Douglas Zatzick S29 Preferences for in-person communication among patients in a multi-center randomized study of in-person versus telephone communication of genetic test results for cancer susceptibility Angela R Bradbury, Linda Patrick-Miller, Brian Egleston, Olufunmilayo I Olopade, Michael J Hall, Mary B Daly, Linda Fleisher, Generosa Grana, Pamela Ganschow, Dominique Fetzer, Amanda Brandt, Dana Farengo-Clark, Andrea Forman, Rikki S Gaber, Cassandra Gulden, Janice Horte, Jessica Long, Rachelle Lorenz Chambers, Terra Lucas, Shreshtha Madaan, Kristin Mattie, Danielle McKenna, Susan Montgomery, Sarah Nielsen, Jacquelyn Powers, Kim Rainey, Christina Rybak, Michelle Savage, Christina Seelaus, Jessica Stoll, Jill Stopfer, Shirley Yao and Susan Domchek S30 Working towards de-implementation: A mixed methods study in breast cancer surveillance care Erin Hahn, Corrine Munoz-Plaza, Jianjin Wang, Jazmine Garcia Delgadillo, Brian Mittman Michael Gould S31Integrating evidence-based practices for increasing cancer screenings in safety-net primary care systems: A multiple case study using the consolidated framework for implementation research Shuting (Lily) Liang, Michelle C. Kegler, Megan Cotter, Emily Phillips, April Hermstad, Rentonia Morton, Derrick Beasley, Jeremy Martinez, Kara Riehman S32 Observations from implementing an mHealth intervention in an FQHC David Gustafson, Lisa Marsch, Louise Mares, Andrew Quanbeck, Fiona McTavish, Helene McDowell, Randall Brown, Chantelle Thomas, Joseph Glass, Joseph Isham, Dhavan Shah S33 A multicomponent intervention to improve primary care provider adherence to chronic opioid therapy guidelines and reduce opioid misuse: A cluster randomized controlled trial protocol Jane Liebschutz, Karen Lasser S34 Implementing collaborative care for substance use disorders in primary care: Preliminary findings from the summit study Katherine Watkins, Allison Ober, Sarah Hunter, Karen Lamp, Brett Ewing S35 Sustaining a task-shifting strategy for blood pressure control in Ghana: A stakeholder analysis Juliet Iwelunmor, Joyce Gyamfi, Sarah Blackstone, Nana Kofi Quakyi, Jacob Plange-Rhule, Gbenga Ogedegbe S36 Contextual adaptation of the consolidated framework for implementation research (CFIR) in a tobacco cessation study in Vietnam Pritika Kumar, Nancy Van Devanter, Nam Nguyen, Linh Nguyen, Trang Nguyen, Nguyet Phuong, Donna Shelley S37 Evidence check: A knowledge brokering approach to systematic reviews for policy Sian Rudge S38 Using Evidence Synthesis to Strengthen Complex Health Systems in Low- and Middle-Income Countries Etienne Langlois S39 Does it matter: timeliness or accuracy of results? The choice of rapid reviews or systematic reviews to inform decision-making Andrea Tricco S40 Evaluation of the veterans choice program using lean six sigma at a VA medical center to identify benefits and overcome obstacles Sherry Ball, Anne Lambert-Kerzner, Christine Sulc, Carol Simmons, Jeneen Shell-Boyd, Taryn Oestreich, Ashley O'Connor, Emily Neely, Marina McCreight, Amy Labebue, Doreen DiFiore, Diana Brostow, P. Michael Ho, David Aron S41 The influence of local context on multi-stakeholder alliance quality improvement activities: A multiple case study Jillian Harvey, Megan McHugh, Dennis Scanlon S42 Increasing physical activity in early care and education: Sustainability via active garden education (SAGE) Rebecca Lee, Erica Soltero, Nathan Parker, Lorna McNeill, Tracey Ledoux S43 Marking a decade of policy implementation: The successes and continuing challenges of a provincial school food and nutrition policy in Canada Jessie-Lee McIsaac, Kate MacLeod, Nicole Ata, Sherry Jarvis, Sara Kirk S44 Use of research evidence among state legislators who prioritize mental health and substance abuse issues Jonathan Purtle, Elizabeth Dodson, Ross Brownson S45 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 1 designs Brian Mittman, Geoffrey Curran S46 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 2 designs Geoffrey Curran S47 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 3 designs Jeffrey Pyne S48 Linking team level implementation leadership and implementation climate to individual level attitudes, behaviors, and implementation outcomes Gregory Aarons, Mark Ehrhart, Elisa Torres S49 Pinpointing the specific elements of local context that matter most to implementation outcomes: Findings from qualitative comparative analysis in the RE-inspire study of VA acute stroke care Edward Miech S50 The GO score: A new context-sensitive instrument to measure group organization level for providing and improving care Edward Miech S51 A research network approach for boosting implementation and improvement Kathleen Stevens, I.S.R.N. Steering Council S52 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - The value of qualitative methods in implementation research Alison Hamilton S53 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Learning evaluation: The role of qualitative methods in dissemination and implementation research Deborah Cohen S54 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Qualitative methods in D&I research Deborah Padgett S55 PANEL: Maps & models: The promise of network science for clinical D&I - Hospital network of sharing patients with acute and chronic diseases in California Alexandra Morshed S56 PANEL: Maps & models: The promise of network science for clinical D&I - The use of social network analysis to identify dissemination targets and enhance D&I research study recruitment for pre-exposure prophylaxis for HIV (PrEP) among men who have sex with men Rupa Patel S57 PANEL: Maps & models: The promise of network science for clinical D&I - Network and organizational factors related to the adoption of patient navigation services among rural breast cancer care providers Beth Prusaczyk S58 A theory of de-implementation based on the theory of healthcare professionals’ behavior and intention (THPBI) and the becker model of unlearning David C. Aron, Divya Gupta, Sherry Ball S59 Observation of registered dietitian nutritionist-patient encounters by dietetic interns highlights low awareness and implementation of evidence-based nutrition practice guidelines Rosa Hand, Jenica Abram, Taylor Wolfram S60 Program sustainability action planning: Building capacity for program sustainability using the program sustainability assessment tool Molly Hastings, Sarah Moreland-Russell S61 A review of D&I study designs in published study protocols Rachel Tabak, Alex Ramsey, Ana Baumann, Emily Kryzer, Katherine Montgomery, Ericka Lewis, Margaret Padek, Byron Powell, Ross Brownson S62 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Model simulation techniques to estimate the cost of implementing foundational public health services Cezar Brian Mamaril, Glen Mays, Keith Branham, Lava Timsina S63 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Inter-organizational network effects on the implementation of public health services Glen Mays, Rachel Hogg S64 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Implementation fidelity, coalition functioning, and community prevention system transformation using communities that care Abigail Fagan, Valerie Shapiro, Eric Brown S65 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Expanding capacity for implementation of communities that care at scale using a web-based, video-assisted training system Kevin Haggerty, David Hawkins S66 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Effects of communities that care on reducing youth behavioral health problems Sabrina Oesterle, David Hawkins, Richard Catalano S68 When interventions end: the dynamics of intervention de-adoption and replacement Virginia McKay, M. Margaret Dolcini, Lee Hoffer S69 Results from next-d: can a disease specific health plan reduce incident diabetes development among a national sample of working-age adults with pre-diabetes? Tannaz Moin, Jinnan Li, O. Kenrik Duru, Susan Ettner, Norman Turk, Charles Chan, Abigail Keckhafer, Robert Luchs, Sam Ho, Carol Mangione S70 Implementing smoking cessation interventions in primary care settings (STOP): using the interactive systems framework Peter Selby, Laurie Zawertailo, Nadia Minian, Dolly Balliunas, Rosa Dragonetti, Sarwar Hussain, Julia Lecce S71 Testing the Getting To Outcomes implementation support intervention in prevention-oriented, community-based settings Matthew Chinman, Joie Acosta, Patricia Ebener, Patrick S Malone, Mary Slaughter S72 Examining the reach of a multi-component farmers’ market implementation approach among low-income consumers in an urban context Darcy Freedman, Susan Flocke, Eunlye Lee, Kristen Matlack, Erika Trapl, Punam Ohri-Vachaspati, Morgan Taggart, Elaine Borawski S73 Increasing implementation of evidence-based health promotion practices at large workplaces: The CEOs Challenge Amanda Parrish, Jeffrey Harris, Marlana Kohn, Kristen Hammerback, Becca McMillan, Peggy Hannon S74 A qualitative assessment of barriers to nutrition promotion and obesity prevention in childcare Taren Swindle, Geoffrey Curran, Leanne Whiteside-Mansell, Wendy Ward S75 Documenting institutionalization of a health communication intervention in African American churches Cheryl Holt, Sheri Lou Santos, Erin Tagai, Mary Ann Scheirer, Roxanne Carter, Janice Bowie, Muhiuddin Haider, Jimmie Slade, Min Qi Wang S76 Reduction in hospital utilization by underserved patients through use of a community-medical home Andrew Masica, Gerald Ogola, Candice Berryman, Kathleen Richter S77 Sustainability of evidence-based lay health advisor programs in African American communities: A mixed methods investigation of the National Witness Project Rachel Shelton, Lina Jandorf, Deborah Erwin S78 Predicting the long-term uninsured population and analyzing their gaps in physical access to healthcare in South Carolina Khoa Truong S79 Using an evidence-based parenting intervention in churches to prevent behavioral problems among Filipino youth: A randomized pilot study Joyce R. Javier, Dean Coffey, Sheree M. Schrager, Lawrence Palinkas, Jeanne Miranda S80 Sustainability of elementary school-based health centers in three health-disparate southern communities Veda Johnson, Valerie Hutcherson, Ruth Ellis S81 Childhood obesity prevention partnership in Louisville: creative opportunities to engage families in a multifaceted approach to obesity prevention Anna Kharmats, Sandra Marshall-King, Monica LaPradd, Fannie Fonseca-Becker S82 Improvements in cervical cancer prevention found after implementation of evidence-based Latina prevention care management program Deanna Kepka, Julia Bodson, Echo Warner, Brynn Fowler S83 The OneFlorida data trust: Achieving health equity through research & training capacity building Elizabeth Shenkman, William Hogan, Folakami Odedina, Jessica De Leon, Monica Hooper, Olveen Carrasquillo, Renee Reams, Myra Hurt, Steven Smith, Jose Szapocznik, David Nelson, Prabir Mandal S84 Disseminating and sustaining medical-legal partnerships: Shared value and social return on investment James Teufel

In the modern era of on-demand ubiquitous computing, where applications and services are deployed in well-provisioned, well-managed infrastructures, administered by large groups of cloud providers such as Amazon, Google, Microsoft, Oracle, etc., performance and dependability of the systems have become primary objectives.Cloud computing has evolved from questioning the Quality-of-Service (QoS) making factors such as availability, reliability, liveness, safety and security, extremely necessary in the complete definition of a system. Indeed, computing systems must be resilient in the presence of failures and attacks to prevent their inaccessibility which can lead to expensive maintenance costs and loss of business. With the growing components in cloud systems, faults occur more commonly resulting in frequent cloud outages and failing to guarantee the QoS. Cloud providers have seen episodic incidents of arbitrary (i.e., Byzantine) faults where systems demonstrate unpredictable conducts, which includes incorrect response of a client's request, sending corrupt messages, intentional delaying of messages, disobeying the ordering of the requests, etc.This has led researchers to extensively study Byzantine Fault Tolerance (BFT) and propose numerous protocols and software prototypes. These BFT solutions not only provide consistent and available services despite arbitrary failures, they also intend to reduce the cost and performance overhead incurred by the underlying systems. However, BFT prototypes have been evaluated in ad-hoc settings, considering either ideal conditions or very limited faulty scenarios. This fails to convince the practitioners for the adoption of BFT protocols in a distributed system. Some argue on the applicability of expensive and complex BFT to tolerate arbitrary faults while others are skeptical on the adeptness of BFT techniques. This thesis precisely addresses this problem and presents a comprehensive benchmarking environment which eases the setup of execution scenarios to analyze and compare the effectiveness and robustness of these existing BFT proposals.Specifically, contributions of this dissertation are as follows.First, we introduce a generic architecture for benchmarking distributed protocols. This architecture, comprises reusable components for building a benchmark for performance and dependability analysis of distributed protocols. The architecture allows defining workload and faultload, and their injection. It also produces performance, dependability, and low-level system and network statistics. Furthermore, the thesis presents the benefits of a general architecture.Second, we present BFT-Bench, the first BFT benchmark, for analyzing and comparing representative BFT protocols under identical scenarios. BFT-Bench allows end-users evaluate different BFT implementations under user-defined faulty behaviors and varying workloads. It allows automatic deploying these BFT protocols in a distributed setting with ability to perform monitoring and reporting of performance and dependability aspects. In our results, we empirically compare some existing state-of-the-art BFT protocols, in various workloads and fault scenarios with BFT-Bench, demonstrating its effectiveness in practice.Overall, this thesis aims to make BFT benchmarking easy to adopt by developers and end-users of BFT protocols.BFT-Bench framework intends to help users to perform efficient comparisons of competing BFT implementations, and incorporating effective solutions to the detected loopholes in the BFT prototypes. Furthermore, this dissertation strengthens the belief in the need of BFT techniques for ensuring correct and continued progress of distributed systems during critical fault occurrence.; A l'ère de l’informatique omniprésente et à la demande, où les applications et les services sont déployés sur des infrastructures bien gérées et approvisionnées par des grands groupes de fournisseurs d’informatique en nuage (Cloud Computing), tels Amazon,Google,Microsoft,Oracle, etc, la performance et la fiabilité de ces systèmes sont devenues des objectifs primordiaux. Cette informatique a rendu particulièrement nécessaire la prise en compte des facteurs de la Qualité de Service (QoS), telles que la disponibilité, la fiabilité, la vivacité, la sureté et la sécurité,dans la définition complète d’un système. En effet, les systèmes informatiques doivent être résistants aussi bien aux défaillances qu’aux attaques et ce, afin d'éviter qu'ils ne deviennent inaccessibles, entrainent des couts de maintenance importants et la perte de parts de marché. L'augmentation de la taille et la complexité des systèmes en nuage rend de plus en plus commun les défauts, augmentant la fréquence des pannes, et n’offrant donc plus la Garantie de Service visée. Les fournisseurs d’informatique en nuage font ainsi face épisodiquement à des fautes arbitraires, dites Byzantines, durant lesquelles les systèmes ont des comportements imprévisibles.Ce constat a amené les chercheurs à s’intéresser de plus en plus à la tolérance aux fautes byzantines (BFT) et à proposer de nombreux prototypes de protocoles et logiciels. Ces solutions de BFT visent non seulement à fournir des services cohérents et continus malgré des défaillances arbitraires, mais cherchent aussi à réduire le coût et l’impact sur les performances des systèmes sous-jacents. Néanmoins les prototypes BFT ont été évalués le plus souvent dans des contextes ad hoc, soit dans des conditions idéales, soit en limitant les scénarios de fautes. C’est pourquoi ces protocoles de BFT n’ont pas réussi à convaincre les professionnels des systèmes distribués de les adopter. Cette thèse entend répondre à ce problème en proposant un environnement complet de banc d’essai dont le but est de faciliter la création de scénarios d'exécution utilisables pour aussi bien analyser que comparer l'efficacité et la robustesse des propositions BFT existantes. Les contributions de cette thèse sont les suivantes :Nous introduisons une architecture générique pour analyser des protocoles distribués. Cette architecture comprend des composants réutilisables permettant la mise en œuvre d’outils de mesure des performances et d’analyse de la fiabilité des protocoles distribués. Cette architecture permet de définir la charge de travail, de défaillance, et l’injection de ces dernières. Elle fournit aussi des statistiques de performance, de fiabilité du système de bas niveau et du réseau. En outre, cette thèse présente les bénéfices d’une architecture générale.Nous présentons BFT-Bench, le premier système de banc d’essai de la BFT, pour l'analyse et la comparaison d’un panel de protocoles BFT utilisés dans des situations identiques. BFT-Bench permet aux utilisateurs d'évaluer des implémentations différentes pour lesquels ils définissent des comportements défaillants avec différentes charges de travail.Il permet de déployer automatiquement les protocoles BFT étudiés dans un environnement distribué et offre la possibilité de suivre et de rendre compte des aspects performance et fiabilité. Parmi nos résultats, nous présentons une comparaison de certains protocoles BFT actuels, réalisée avec BFT-Bench, en définissant différentes charges de travail et différents scénarii de fautes. Cette réelle application de BFT-Bench en démontre l’efficacité.Le logiciel BFT-Bench a été conçu en ce sens pour aider les utilisateurs à comparer efficacement différentes implémentations de BFT et apporter des solutions effectives aux lacunes identifiées des prototypes BFT. De plus, cette thèse défend l’idée que les techniques BFT sont nécessaires pour assurer un fonctionnement continu et correct des systèmes distribués confrontés à des situations critiques.

In the modern era of on-demand ubiquitous computing, where applications and services are deployed in well-provisioned, well-managed infrastructures, administered by large groups of cloud providers such as Amazon, Google, Microsoft, Oracle, etc., performance and dependability of the systems have become primary objectives.Cloud computing has evolved from questioning the Quality-of-Service (QoS) making factors such as availability, reliability, liveness, safety and security, extremely necessary in the complete definition of a system. Indeed, computing systems must be resilient in the presence of failures and attacks to prevent their inaccessibility which can lead to expensive maintenance costs and loss of business. With the growing components in cloud systems, faults occur more commonly resulting in frequent cloud outages and failing to guarantee the QoS. Cloud providers have seen episodic incidents of arbitrary (i.e., Byzantine) faults where systems demonstrate unpredictable conducts, which includes incorrect response of a client's request, sending corrupt messages, intentional delaying of messages, disobeying the ordering of the requests, etc.This has led researchers to extensively study Byzantine Fault Tolerance (BFT) and propose numerous protocols and software prototypes. These BFT solutions not only provide consistent and available services despite arbitrary failures, they also intend to reduce the cost and performance overhead incurred by the underlying systems. However, BFT prototypes have been evaluated in ad-hoc settings, considering either ideal conditions or very limited faulty scenarios. This fails to convince the practitioners for the adoption of BFT protocols in a distributed system. Some argue on the applicability of expensive and complex BFT to tolerate arbitrary faults while others are skeptical on the adeptness of BFT techniques. This thesis precisely addresses this problem and presents a comprehensive benchmarking environment which eases the setup of execution scenarios to analyze and compare the effectiveness and robustness of these existing BFT proposals.Specifically, contributions of this dissertation are as follows.First, we introduce a generic architecture for benchmarking distributed protocols. This architecture, comprises reusable components for building a benchmark for performance and dependability analysis of distributed protocols. The architecture allows defining workload and faultload, and their injection. It also produces performance, dependability, and low-level system and network statistics. Furthermore, the thesis presents the benefits of a general architecture.Second, we present BFT-Bench, the first BFT benchmark, for analyzing and comparing representative BFT protocols under identical scenarios. BFT-Bench allows end-users evaluate different BFT implementations under user-defined faulty behaviors and varying workloads. It allows automatic deploying these BFT protocols in a distributed setting with ability to perform monitoring and reporting of performance and dependability aspects. In our results, we empirically compare some existing state-of-the-art BFT protocols, in various workloads and fault scenarios with BFT-Bench, demonstrating its effectiveness in practice.Overall, this thesis aims to make BFT benchmarking easy to adopt by developers and end-users of BFT protocols.BFT-Bench framework intends to help users to perform efficient comparisons of competing BFT implementations, and incorporating effective solutions to the detected loopholes in the BFT prototypes. Furthermore, this dissertation strengthens the belief in the need of BFT techniques for ensuring correct and continued progress of distributed systems during critical fault occurrence.; A l'ère de l’informatique omniprésente et à la demande, où les applications et les services sont déployés sur des infrastructures bien gérées et approvisionnées par des grands groupes de fournisseurs d’informatique en nuage (Cloud Computing), tels Amazon,Google,Microsoft,Oracle, etc, la performance et la fiabilité de ces systèmes sont devenues des objectifs primordiaux. Cette informatique a rendu particulièrement nécessaire la prise en compte des facteurs de la Qualité de Service (QoS), telles que la disponibilité, la fiabilité, la vivacité, la sureté et la sécurité,dans la définition complète d’un système. En effet, les systèmes informatiques doivent être résistants aussi bien aux défaillances qu’aux attaques et ce, afin d'éviter qu'ils ne deviennent inaccessibles, entrainent des couts de maintenance importants et la perte de parts de marché. L'augmentation de la taille et la complexité des systèmes en nuage rend de plus en plus commun les défauts, augmentant la fréquence des pannes, et n’offrant donc plus la Garantie de Service visée. Les fournisseurs d’informatique en nuage font ainsi face épisodiquement à des fautes arbitraires, dites Byzantines, durant lesquelles les systèmes ont des comportements imprévisibles.Ce constat a amené les chercheurs à s’intéresser de plus en plus à la tolérance aux fautes byzantines (BFT) et à proposer de nombreux prototypes de protocoles et logiciels. Ces solutions de BFT visent non seulement à fournir des services cohérents et continus malgré des défaillances arbitraires, mais cherchent aussi à réduire le coût et l’impact sur les performances des systèmes sous-jacents. Néanmoins les prototypes BFT ont été évalués le plus souvent dans des contextes ad hoc, soit dans des conditions idéales, soit en limitant les scénarios de fautes. C’est pourquoi ces protocoles de BFT n’ont pas réussi à convaincre les professionnels des systèmes distribués de les adopter. Cette thèse entend répondre à ce problème en proposant un environnement complet de banc d’essai dont le but est de faciliter la création de scénarios d'exécution utilisables pour aussi bien analyser que comparer l'efficacité et la robustesse des propositions BFT existantes. Les contributions de cette thèse sont les suivantes :Nous introduisons une architecture générique pour analyser des protocoles distribués. Cette architecture comprend des composants réutilisables permettant la mise en œuvre d’outils de mesure des performances et d’analyse de la fiabilité des protocoles distribués. Cette architecture permet de définir la charge de travail, de défaillance, et l’injection de ces dernières. Elle fournit aussi des statistiques de performance, de fiabilité du système de bas niveau et du réseau. En outre, cette thèse présente les bénéfices d’une architecture générale.Nous présentons BFT-Bench, le premier système de banc d’essai de la BFT, pour l'analyse et la comparaison d’un panel de protocoles BFT utilisés dans des situations identiques. BFT-Bench permet aux utilisateurs d'évaluer des implémentations différentes pour lesquels ils définissent des comportements défaillants avec différentes charges de travail.Il permet de déployer automatiquement les protocoles BFT étudiés dans un environnement distribué et offre la possibilité de suivre et de rendre compte des aspects performance et fiabilité. Parmi nos résultats, nous présentons une comparaison de certains protocoles BFT actuels, réalisée avec BFT-Bench, en définissant différentes charges de travail et différents scénarii de fautes. Cette réelle application de BFT-Bench en démontre l’efficacité.Le logiciel BFT-Bench a été conçu en ce sens pour aider les utilisateurs à comparer efficacement différentes implémentations de BFT et apporter des solutions effectives aux lacunes identifiées des prototypes BFT. De plus, cette thèse défend l’idée que les techniques BFT sont nécessaires pour assurer un fonctionnement continu et correct des systèmes distribués confrontés à des situations critiques.

Recently, candidate constructions were given for indistinguishability obfuscation by Garg, Gentry, Halevi, Raykova, Sahai, and Waters [FOCS'13]. The goal of general-purpose program obfuscation is to make an arbitrary computer program ``unintelligible'' while preserving its functionality. Since then, this new tool has been used to obtain many new applications. In this dissertation, we study the problem of protecting software against new and powerful adversary structures as well as optimize the efficiency of secure general-purpose obfuscation schemes.In the first part of this dissertation, we initiate the study of hosting services on an untrusted cloud. Specifically, we consider a scenario where a service provider has created a software service S and desires to outsource the execution of this service to an untrusted cloud. The software service contains secrets that the provider would like to keep hidden from the cloud. For example, the software might contain a secret database, and the service could allowusers to make queries to different slices of this database depending on the user's identity. Furthermore, we seek to protect knowledge of the software S to the maximum extent possible even if the cloud can collude with several corrupted users. We provide the first formalizations of security for this setting, and construction relying on indistinguishabilityobfuscation.The great interest in the utility of obfuscation leads to a natural and pressing goal: to improve the efficiency of general-purpose obfuscation. In the second part of this dissertation, we initiate the work to optimize the efficiency of secure general-purpose obfuscation schemes.We focus on the problem of optimizing the obfuscation of Boolean formulas and branchingprograms - this corresponds to optimizing the ``core obfuscator'' from the work of Garg \etal, and all subsequent works constructing general-purpose obfuscators. Our efficiency improvement is obtained by generalizing the class of branching programs that can be directly obfuscated. This generalization allows us to achieve a simple simulation of formulas by branching programs while avoiding the use of Barrington's theorem, on which all previous constructions relied. Furthermore, the ability to directly obfuscate general branching programs (without bootstrapping) allows us to efficiently apply our construction to naturalfunction classes that are not known to have polynomial-size formulas.

BACKGROUND Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P amp;lt; 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.) Funding Agencies|Tesaro; Amgen; Genentech; Roche; AstraZeneca; Myriad Genetics; Merck; Gradalis; Cerulean; Vermillion; ImmunoGen; Pfizer; Bayer; Nu-Cana BioMed; INSYS Therapeutics; GlaxoSmithKline; Verastem; Mateon Therapeutics; Pharmaceutical Product Development; Clovis Oncology; Janssen/Johnson Johnson; Eli Lilly; Merck Sharp Dohme

Industrial growth, urbanization and wrong agricultural practices are responsible for pollution and loss of environmental quality. Petro plastics, produced from mineral resources, are one of the most important materials, but the production process destructs the environment. Bio-based and biodegradable plastics can form the basis for environmentally preferable and sustainable alternative to current materials based exclusively on petroleum feed stocks. Bioplastic helps us to overcome the problem of pollution caused by synthetic plastics as they originate from renewable resources and are a new generation of plastics able to significantly reduce the environmental impact in terms of energy consumption and greenhouse effect. Polyhydroxyalkanoate (PHA) emerges as a potential candidate in a way to be used as a biopolymer material which not only possesses the characteristic similar to the traditional plastic, but it is also biodegradable in nature without any toxic production .A way to reduce the production cost is the use of alternative substrates, such as the agro industrial wastes. This review gives an overview of economical strategies to reduce production costs of PHA as well as its applications in various fields.

In this work, we consider the long-standing open question of constructing constant-round concurrent zero-knowledge protocols in the plain model. Resolving this question is known to require non-black-box techniques. We consider non-black-box techniques for zero-knowledge based on knowledge assumptions, a line of thinking initiated by the work of Hada and Tanaka (CRYPTO 1998). Prior to our work, it was not known whether knowledge assumptions could be used for achieving security in the concurrent setting, due to a number of significant limitations that we discuss here. Nevertheless, we obtain the following results: 1. We obtain the first constant round concurrent zero-knowledge argument for \textbf{NP} in the plain model based on a new variant of knowledge of exponent assumption. Furthermore, our construction avoids the inefficiency inherent in previous non-black-box techniques such that those of Barak (FOCS 2001); we obtain our result through an efficient protocol compiler. 2. Unlike Hada and Tanaka, we do not require a knowledge assumption to argue the soundness of our protocol. Instead, we use a discrete log like assumption, which we call Diffie-Hellman Logarithm Assumption, to prove the soundness of our protocol. 3. We give evidence that our new variant of knowledge of exponent assumption is in fact plausible. In particular, we show that our assumption holds in the generic group model. 4. Knowledge assumptions are especially delicate assumptions whose plausibility may be hard to gauge. We give a novel framework to express knowledge assumptions in a more flexible way, which may allow for formulation of plausible assumptions and exploration of their impact and application in cryptography., 30 pages, 3 figures

We study the Unsplittable Flow Problem (UFP) and related variants, namely UFP with Bag Constraints and UFP with Rounds, on paths and trees. We provide improved constant factor approximation algorithms for all these problems under the no bottleneck assumption (NBA), which says that the maximum demand for any source-sink pair is at most the minimum capacity of any edge. We obtain these improved results by expressing a feasible solution to a natural LP relaxation of the UFP as a near-convex combination of feasible integral solutions.

Penetrating neck injuries are dangerous and deserve emergency treatment by virtue of the vital structures present underneath. There is a potential risk of unrecognized vascular injury and retained foreign bodies with their associated complications in these wounds. Therefore, an early diagnostic workup to localize the site of injury and an immediate neck exploration are important.

Augmented reality provides its user with additional information not available through the natural real-world environment. This additional information displayed to the user potentially poses a risk of perceptual and cognitive load and vision-based difficulties. The presence of real-world objects together with virtual augmenting information requires the user to repeatedly switch eye focus between the two in order to extract information from both environments. Switching eye focus may result in additional time on user tasks and lower task accuracy. Thus, one of the goals of this research was to understand the impact of switching eye focus between real-world and virtual information on user task performance. Secondly, focus depth, which is an important parameter and a depth cue, may affect the user's view of the augmented world. If focus depth is not adjusted properly, it may result in vision-based difficulties and reduce speed, accuracy, and comfort while using an augmented reality display. Thus, the second goal of this thesis was to study the effect of focus depth on task performance in augmented reality systems. In augmented reality environments, real-world and virtual information are found at different distances from the user. To focus at different depths, the user's eye needs to accommodate and converge, which may strain the eye and degrade performance on tasks. However, no research in augmented reality has explored this issue. Hence, the third goal of this thesis was to determine if distance of virtual information from the user impacts task performance. To accomplish these goals, a 3x3x3 within subjects design was used. The experimental task for the study required the user to repeatedly switch eye focus between the virtual text and real-world text. A monocular see-through head- mounted display was used for this research. Results of this study revealed that switching between real-world and virtual information in augmented reality is extremely difficult when information is displayed at optical infinity. Virtual information displayed at optical infinity may be unsuitable for tasks of the nature used in this research. There was no impact of focus depth on user task performance and hence it is preliminarily recommended that manufacturers of head-mounted displays may only need to make fixed focus depth displays; this clearly merits additional intensive research. Further, user task performance was better when focus depth, virtual information, and real-world information were all at the same distance from the user as compared to conditions when they were mismatched. Based on this result we recommend presenting virtual information at the same distance as real-world information of interest. Master of Science